Novel therapy for atopic dermatitis Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects over 15 million Americans. Severe AD results in skin damage that increases the risk for secondary infections. Mild AD is treated with topical anti-pruritics and anti-inflammatory steroids. Moderate-to-severe AD, however, often requires systemic therapy. Current therapies, including anti-IgE, are either ineffective or have adverse effects. Recent studies have demonstrated the involvement of novel cytokines IL-33 and IL-36 in initiating and maintaining inflammatory processes in AD. Activation of inflammatory pathways by IL-1, IL-33, or IL-36 requires the IL-1 receptor accessory protein (IL1RAP, IL1RAcP). We have identified a high-affinity murine monoclonal antibody to IL1RAP and have demonstrated its ability to block IL-1, IL-33, and IL-36 signaling in vitro and in vivo. We propose to develop this lead as a best-in-class therapy for allergic inflammation. Anti-IL1RAP is expected to specifically target inflammatory zones where IL1RAP is up-regulated and to be more selective and less toxic than current therapies.